| 1. |
- Sliz, E., et al.
(författare)
-
Evidence of a causal effect of genetic tendency to gain muscle mass on uterine leiomyomata
- 2023
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1
-
Tidskriftsartikel (refereegranskat)abstract
- Uterine leiomyomata (UL) are the most common tumours of the female genital tract and the primary cause of surgical removal of the uterus. Genetic factors contribute to UL susceptibility. To add understanding to the heritable genetic risk factors, we conduct a genome-wide association study (GWAS) of UL in up to 426,558 European women from FinnGen and a previous UL meta-GWAS. In addition to the 50 known UL loci, we identify 22 loci that have not been associated with UL in prior studies. UL-associated loci harbour genes enriched for development, growth, and cellular senescence. Of particular interest are the smooth muscle cell differentiation and proliferation-regulating genes functioning on the myocardin-cyclin dependent kinase inhibitor 1A pathway. Our results further suggest that genetic predisposition to increased fat-free mass may be causally related to higher UL risk, underscoring the involvement of altered muscle tissue biology in UL pathophysiology. Overall, our findings add to the understanding of the genetic pathways underlying UL, which may aid in developing novel therapeutics.
|
|
| 2. |
- Bauer, M., et al.
(författare)
-
Association between polarity of first episode and solar insolation in bipolar I disorder
- 2022
-
Ingår i: Journal of Psychosomatic Research. - : Elsevier BV. - 0022-3999 .- 1879-1360. ; 160
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: Circadian rhythm disruption is commonly observed in bipolar disorder (BD). Daylight is the most powerful signal to entrain the human circadian clock system. This exploratory study investigated if solar insolation at the onset location was associated with the polarity of the first episode of BD I. Solar insolation is the amount of electromagnetic energy from the Sun striking a surface area of the Earth. Methods: Data from 7488 patients with BD I were collected at 75 sites in 42 countries. The first episode occurred at 591 onset locations in 67 countries at a wide range of latitudes in both hemispheres. Solar insolation values were obtained for every onset location, and the ratio of the minimum mean monthly insolation to the maximum mean monthly insolation was calculated. This ratio is largest near the equator (with little change in solar insolation over the year), and smallest near the poles (where winter insolation is very small compared to summer insolation). This ratio also applies to tropical locations which may have a cloudy wet and clear dry season, rather than winter and summer. Results: The larger the change in solar insolation throughout the year (smaller the ratio between the minimum monthly and maximum monthly values), the greater the likelihood the first episode polarity was depression. Other associated variables were being female and increasing percentage of gross domestic product spent on country health expenditures. (All coefficients: P ≤ 0.001). Conclusion: Increased awareness and research into circadian dysfunction throughout the course of BD is warranted.
|
|
| 3. |
- Bauer, M., et al.
(författare)
-
Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder
- 2021
-
Ingår i: International Journal of Bipolar Disorders. - : Springer Science and Business Media LLC. - 2194-7511. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Background Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun's electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed.
|
|
| 4. |
- Bauer, M., et al.
(författare)
-
Exploratory study of ultraviolet B (UVB) radiation and age of onset of bipolar disorder
- 2023
-
Ingår i: International Journal of Bipolar Disorders. - 2194-7511. ; 11:1
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundSunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample.MethodsData for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P <= 0.001.ResultsThe 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger.ConclusionUVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.
|
|
| 5. |
- Bauer, M., et al.
(författare)
-
Solar insolation in springtime influences age of onset of bipolar I disorder
- 2017
-
Ingår i: Acta Psychiatrica Scandinavica. - : Wiley. - 0001-690X .- 1600-0447. ; 136:6, s. 571-582
-
Forskningsöversikt (refereegranskat)abstract
- Objective: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder. Method: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries. Variables included solar insolation, birth-cohort, family history, polarity of first episode and country physician density. Results: There was a significant, inverse association between the maximum monthly increase in solar insolation at the onset location, and the age of onset. This effect was reduced in those without a family history of mood disorders and with a first episode of mania rather than depression. The maximum monthly increase occurred in springtime. The youngest birth-cohort had the youngest age of onset. All prior relationships were confirmed using both the entire sample, and only the youngest birth-cohort (all estimated coefficients P < 0.001). Conclusion: A large increase in springtime solar insolation may impact the onset of bipolar disorder, especially with a family history of mood disorders. Recent societal changes that affect light exposure (LED lighting, mobile devices backlit with LEDs) may influence adaptability to a springtime circadian challenge.
|
|
| 6. |
- Kivimäki, M., et al.
(författare)
-
Job strain as a risk factor for coronary heart disease : A collaborative meta-analysis of individual participant data
- 2012
-
Ingår i: The Lancet. - : Elsevier. - 0140-6736 .- 1474-547X. ; 380:9852, s. 1491-1497
-
Tidskriftsartikel (refereegranskat)abstract
- Background Published work assessing psychosocial stress (job strain) as a risk factor for coronary heart disease is inconsistent and subject to publication bias and reverse causation bias. We analysed the relation between job strain and coronary heart disease with a meta-analysis of published and unpublished studies. Methods We used individual records from 13 European cohort studies (1985-2006) of men and women without coronary heart disease who were employed at time of baseline assessment. We measured job strain with questions from validated job-content and demand-control questionnaires. We extracted data in two stages such that acquisition and harmonisation of job strain measure and covariables occurred before linkage to records for coronary heart disease. We defined incident coronary heart disease as the first non-fatal myocardial infarction or coronary death. Findings 30 214 (15%) of 197 473 participants reported job strain. In 1•49 million person-years at risk (mean follow-up 7•5 years [SD 1•7]), we recorded 2358 events of incident coronary heart disease. After adjustment for sex and age, the hazard ratio for job strain versus no job strain was 1•23 (95% CI 1•10-1•37). This effect estimate was higher in published (1•43, 1•15-1•77) than unpublished (1•16, 1•02-1•32) studies. Hazard ratios were likewise raised in analyses addressing reverse causality by exclusion of events of coronary heart disease that occurred in the first 3 years (1•31, 1•15-1•48) and 5 years (1•30, 1•13-1•50) of follow-up. We noted an association between job strain and coronary heart disease for sex, age groups, socioeconomic strata, and region, and after adjustments for socioeconomic status, and lifestyle and conventional risk factors. The population attributable risk for job strain was 3•4%. Interpretation Our findings suggest that prevention of workplace stress might decrease disease incidence; however, this strategy would have a much smaller effect than would tackling of standard risk factors, such as smoking. Funding Finnish Work Environment Fund, the Academy of Finland, the Swedish Research Council for Working Life and Social Research, the German Social Accident Insurance, the Danish National Research Centre for the Working Environment, the BUPA Foundation, the Ministry of Social Affairs and Employment, the Medical Research Council, the Wellcome Trust, and the US National Institutes of Health.
|
|
| 7. |
|
|
| 8. |
- Heikkila, K., et al.
(författare)
-
Job strain and the risk of severe asthma exacerbations : a meta-analysis of individual-participant data from 100 000 European men and women
- 2014
-
Ingår i: Allergy. European Journal of Allergy and Clinical Immunology. - : Wiley. - 0105-4538 .- 1398-9995. ; 69:6, s. 775-783
-
Tidskriftsartikel (refereegranskat)abstract
- BackgroundMany patients and healthcare professionals believe that work-related psychosocial stress, such as job strain, can make asthma worse, but this is not corroborated by empirical evidence. We investigated the associations between job strain and the incidence of severe asthma exacerbations in working-age European men and women. MethodsWe analysed individual-level data, collected between 1985 and 2010, from 102 175 working-age men and women in 11 prospective European studies. Job strain (a combination of high demands and low control at work) was self-reported at baseline. Incident severe asthma exacerbations were ascertained from national hospitalization and death registries. Associations between job strain and asthma exacerbations were modelled using Cox regression and the study-specific findings combined using random-effects meta-analyses. ResultsDuring a median follow-up of 10years, 1 109 individuals experienced a severe asthma exacerbation (430 with asthma as the primary diagnostic code). In the age- and sex-adjusted analyses, job strain was associated with an increased risk of severe asthma exacerbations defined using the primary diagnostic code (hazard ratio, HR: 1.27, 95% confidence interval, CI: 1.00, 1.61). This association attenuated towards the null after adjustment for potential confounders (HR: 1.22, 95% CI: 0.96, 1.55). No association was observed in the analyses with asthma defined using any diagnostic code (HR: 1.01, 95% CI: 0.86, 1.19). ConclusionsOur findings suggest that job strain is probably not an important risk factor for severe asthma exacerbations leading to hospitalization or death.
|
|
| 9. |
|
|
| 10. |
- Theorell, Töres, et al.
(författare)
-
Job strain in relation to body mass index : pooled analysis of 160 000 adults from 13 cohort studies
- 2012
-
Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 272:1, s. 65-73
-
Tidskriftsartikel (refereegranskat)abstract
- Job strain in relation to body mass index: pooled analysis of 160 000 adults from 13 cohort studies. J Intern Med 2012; 272: 6573. Background. Evidence of an association between job strain and obesity is inconsistent, mostly limited to small-scale studies, and does not distinguish between categories of underweight or obesity subclasses. Objectives. To examine the association between job strain and body mass index (BMI) in a large adult population. Methods. We performed a pooled cross-sectional analysis based on individual-level data from 13 European studies resulting in a total of 161 746 participants (49% men, mean age, 43.7 years). Longitudinal analysis with a median follow-up of 4 years was possible for four cohort studies (n = 42 222). Results. A total of 86 429 participants were of normal weight (BMI 18.524.9 kg m-2), 2149 were underweight (BMI < 18.5 kg m-2), 56 572 overweight (BMI 25.029.9 kg m-2) and 13 523 class I (BMI 3034.9 kg m-2) and 3073 classes II/III (BMI = 35 kg m-2) obese. In addition, 27 010 (17%) participants reported job strain. In cross-sectional analyses, we found increased odds of job strain amongst underweight [odds ratio 1.12, 95% confidence interval (CI) 1.001.25], obese class I (odds ratio 1.07, 95% CI 1.021.12) and obese classes II/III participants (odds ratio 1.14, 95% CI 1.011.28) as compared with participants of normal weight. In longitudinal analysis, both weight gain and weight loss were related to the onset of job strain during follow-up. Conclusions. In an analysis of European data, we found both weight gain and weight loss to be associated with the onset of job strain, consistent with a U-shaped cross-sectional association between job strain and BMI. These associations were relatively modest; therefore, it is unlikely that intervention to reduce job strain would be effective in combating obesity at a population level.
|
|
